It is hypothesized that: (a) several discrepancies in digoxin pharmacokinetics, (b) part of the intersubject variability in digoxin serum or plasma concentrations, and (c) part of the problem in separating toxic and nontoxic patients taking digoxin on the basis of serum digoxin concentrations are most probably the consequence of the non-specificity of the radioimmunoassay (RIA) methods - i.e., measurement of not only unchanged digoxin but also digoxin metabolites by the RIA. A proposed study in normal volunteers and another study in adult cardiac patients taking digoxin chronically will test these hypotheses. A third study will allow measurement of both atrial digoxin concentrations, plasma concentrations, and the atrial tissue/plasma concentration ratios in children 6 months to 15 years of age, where the atrial tissue is taken during routine procedures in open heart surgery; such measurements have been made in infants and adults by means of non-specific assay methods, but not in children in the age range indicated, and, in patients of any age by a specific method of assay. In the three human studies each plasma, urine and atrial tissue sample will be assayed for digoxin by both the nonspecific RIA method and by a specific method which involves high-performance liquid chromatographic (HPLC) separation of the digoxin from its metabolites first, followed by radioimmunoassay. Results of these studies should elucidate some of the vexatious problems which have arisen during human investigations where only the RIA has been applied.